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Entropic control of the free-energy landscape of an archetypal biomolecular machine

Biomolecular machines are complex macromolecular assemblies that utilize thermal and chemical energy to perform essential, multistep, cellular processes. Despite possessing different architectures and functions, an essential feature of the mechanisms of action of all such machines is that they requi...

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Autores principales: Ray, Korak Kumar, Kinz-Thompson, Colin D., Fei, Jingyi, Wang, Bin, Lin, Qiao, Gonzalez, Ruben L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214133/
https://www.ncbi.nlm.nih.gov/pubmed/37186858
http://dx.doi.org/10.1073/pnas.2220591120
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author Ray, Korak Kumar
Kinz-Thompson, Colin D.
Fei, Jingyi
Wang, Bin
Lin, Qiao
Gonzalez, Ruben L.
author_facet Ray, Korak Kumar
Kinz-Thompson, Colin D.
Fei, Jingyi
Wang, Bin
Lin, Qiao
Gonzalez, Ruben L.
author_sort Ray, Korak Kumar
collection PubMed
description Biomolecular machines are complex macromolecular assemblies that utilize thermal and chemical energy to perform essential, multistep, cellular processes. Despite possessing different architectures and functions, an essential feature of the mechanisms of action of all such machines is that they require dynamic rearrangements of structural components. Surprisingly, biomolecular machines generally possess only a limited set of such motions, suggesting that these dynamics must be repurposed to drive different mechanistic steps. Although ligands that interact with these machines are known to drive such repurposing, the physical and structural mechanisms through which ligands achieve this remain unknown. Using temperature-dependent, single-molecule measurements analyzed with a time-resolution-enhancing algorithm, here, we dissect the free-energy landscape of an archetypal biomolecular machine, the bacterial ribosome, to reveal how its dynamics are repurposed to drive distinct steps during ribosome-catalyzed protein synthesis. Specifically, we show that the free-energy landscape of the ribosome encompasses a network of allosterically coupled structural elements that coordinates the motions of these elements. Moreover, we reveal that ribosomal ligands which participate in disparate steps of the protein synthesis pathway repurpose this network by differentially modulating the structural flexibility of the ribosomal complex (i.e., the entropic component of the free-energy landscape). We propose that such ligand-dependent entropic control of free-energy landscapes has evolved as a general strategy through which ligands may regulate the functions of all biomolecular machines. Such entropic control is therefore an important driver in the evolution of naturally occurring biomolecular machines and a critical consideration for the design of synthetic molecular machines.
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spelling pubmed-102141332023-11-15 Entropic control of the free-energy landscape of an archetypal biomolecular machine Ray, Korak Kumar Kinz-Thompson, Colin D. Fei, Jingyi Wang, Bin Lin, Qiao Gonzalez, Ruben L. Proc Natl Acad Sci U S A Biological Sciences Biomolecular machines are complex macromolecular assemblies that utilize thermal and chemical energy to perform essential, multistep, cellular processes. Despite possessing different architectures and functions, an essential feature of the mechanisms of action of all such machines is that they require dynamic rearrangements of structural components. Surprisingly, biomolecular machines generally possess only a limited set of such motions, suggesting that these dynamics must be repurposed to drive different mechanistic steps. Although ligands that interact with these machines are known to drive such repurposing, the physical and structural mechanisms through which ligands achieve this remain unknown. Using temperature-dependent, single-molecule measurements analyzed with a time-resolution-enhancing algorithm, here, we dissect the free-energy landscape of an archetypal biomolecular machine, the bacterial ribosome, to reveal how its dynamics are repurposed to drive distinct steps during ribosome-catalyzed protein synthesis. Specifically, we show that the free-energy landscape of the ribosome encompasses a network of allosterically coupled structural elements that coordinates the motions of these elements. Moreover, we reveal that ribosomal ligands which participate in disparate steps of the protein synthesis pathway repurpose this network by differentially modulating the structural flexibility of the ribosomal complex (i.e., the entropic component of the free-energy landscape). We propose that such ligand-dependent entropic control of free-energy landscapes has evolved as a general strategy through which ligands may regulate the functions of all biomolecular machines. Such entropic control is therefore an important driver in the evolution of naturally occurring biomolecular machines and a critical consideration for the design of synthetic molecular machines. National Academy of Sciences 2023-05-15 2023-05-23 /pmc/articles/PMC10214133/ /pubmed/37186858 http://dx.doi.org/10.1073/pnas.2220591120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Ray, Korak Kumar
Kinz-Thompson, Colin D.
Fei, Jingyi
Wang, Bin
Lin, Qiao
Gonzalez, Ruben L.
Entropic control of the free-energy landscape of an archetypal biomolecular machine
title Entropic control of the free-energy landscape of an archetypal biomolecular machine
title_full Entropic control of the free-energy landscape of an archetypal biomolecular machine
title_fullStr Entropic control of the free-energy landscape of an archetypal biomolecular machine
title_full_unstemmed Entropic control of the free-energy landscape of an archetypal biomolecular machine
title_short Entropic control of the free-energy landscape of an archetypal biomolecular machine
title_sort entropic control of the free-energy landscape of an archetypal biomolecular machine
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214133/
https://www.ncbi.nlm.nih.gov/pubmed/37186858
http://dx.doi.org/10.1073/pnas.2220591120
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